Review of effects of anti-VEGF treatment on refractive error

Figures & data

Table 1 Reports of refractive error after the use of anti-vascular endothelial growth factor agents for the treatment of retinopathy of prematurity

Study	Location	Mean GA (weeks)	Mean BW (g)	Mean AA at Tx (weeks)	Refracted eyes, n	Refraction age (months)	Anti-VEGF, dose (mg)	Mean SE ± SD (D), anti-VEGF Tx	Mean SE ± SD (D), laser Tx
Wu et al^Citation20	Taiwan	26.3 IVB	930.1 IVB	36.6 IVB	53 IVB 14 IVB + CLT	17.8	IVB, 0.625	−0.1±1.8	NA
Martínez-Castellanos et al^Citation21	Mexico	29.3 IVB	1,233.3 IVB	25.2 IVB	9 IVB	60	IVB, 1.25	−1.75	NA
Harder et al^Citation22	Germany	25.2 IVB 25.3 CLT	622 IVB 717 CLT	25.2 IVB 25.3 CLT	23 IVB 26 CLT	11.4	IVB, 0.375 or 0.625	−1.04±4.24	−4.41±5.5
Chen et al^Citation23	Taiwan	26.4 IVB	882.2 IVB	35	40 IVB 17 IVB + CLT	24	IVB, 0.625	−0.98±4.05	IVB + CLT: −2.4
Geloneck et al^Citation1	USA	24.4 IVB 24.2 CLT	652.1 IVB 669.3 CLT	35.1 IVB 34.8 CLT	110 IVB 101 CLT	30 IVB 30 CLT	IVB, 0.625	Zone I: −1.51±3.42 Zone II: −0.58±2.53	Zone I: −8.44±7.57 Zone II: −5.83±5.87
Salman and Said^Citation24	Egypt	26.3 IVA	991 IVA	NA	26 IVA	12	IVA, 1	0.75	NA
Isaac et al^Citation25	Canada	25.2 IVB 25 CLT	722 IVB 674 CLT	37.6 IVB 36.7 CLT	23 IVB 22 CLT	12	IVB, 0.625	−3.57±6.19	−6.39±4.41
Kuo et al^Citation26	Taiwan	NA	NA	NA	14 IVB 15 CLT	36	NA	−1.53±2.2	−1.71±1.27
Chen et al^Citation27	Taiwan	26.5 IVB 26.2 IVR	869.1 IVB 848.8 IVR	36.8 IVB 36.4 IVR	41 IVB 31 IVR	12	IVB, 0.625 IVR, 0.25	−0.3 IVB +0.1 IVR	iVB + CLT: −2.4
Hwang et al^Citation28	USA	24.2 IVB 24.8 CLT	668.1 IVB 701.4 CLT	35.1 IVB 36.1 CLT	22 IVB 32 CLT	22.4 IVB 37.1 CLT	IVB, 0.625	−2.4 (zone I, −3.7; zone II, 0.6)	−5.3 (zone I, −10.1; zone II, −4.7)
Gunay et al^Citation29	Brazil	26.4 IVB 27.3 CLT	901.4 IVB 941 CLT	34.0 IVB 33.9 CLT	43 IVB 35 CLT	24	IVB, 0.625	0.42±3.42	−6.66±4.96

Abbreviations: CLT, conventional laser therapy; IVB, intravitreal bevacizumab; IVR, intravitreal ranibizumab; IVA, intravitreal aflibercept; GA, gestational age; BW, birth weight; AA, adjusted age; Tx, treatment; SD, standard deviation; SE, spherical equivalent refractive error; NA, not available.

Figure 1 Zone I distribution of refractive error by treatment modality.

Notes: Distribution of spherical equivalent refractive error at age 2.5 years in eyes that received treatment for stage 3+ retinopathy of prematurity or aggressive posterior retinopathy of prematurity in the Bevacizumab Eliminates the Angiogenic Threat for Retinopathy of Prematurity clinical trial.¹ Data presented according to treatment modality: red, laser without recurrence; brown, laser with recurrence; light blue, intravitreal bevacizumab without recurrence; dark blue, intravitreal bevacizumab with recurrence. Reproduced with permission from JAMA Ophthalmol. 2014;132(11):1327–1333. Copyright ©2014 American Medical Association. All rights reserved.¹

Figure 2 Zone II posterior distribution of refractive error by treatment modality.

Notes: Distribution of spherical equivalent refractive error at age 2.5 years in eyes that received treatment for stage 3+ retinopathy of prematurity or aggressive posterior retinopathy of prematurity in the Bevacizumab Eliminates the Angiogenic Threat for Retinopathy of Prematurity clinical trial.¹ Data presented according to treatment modality: red, laser without recurrence; brown, laser with recurrence; light blue, intravitreal bevacizumab without recurrence; dark blue, intravitreal bevacizumab with recurrence. Reproduced with permission from JAMA Ophthalmol. 2014;132(11):1327–1333. Copyright © 2014 American Medical Association. All rights reserved.¹

Table 2 Cycloplegic retinoscopic refractive error at age 2.5 years in the Bevacizumab Eliminates the Angiogenic Threat for Retinopathy of Prematurity clinical trial¹

Spherical equivalent refractions, D	Intravitreal bevacizumab		Laser
	Without recurrence	With recurrence	Without recurrence	With recurrence
Zone I (87 eyes)*	50 eyes	2 eyes	26 eyes	9 eyes
Mean (SD)	−1.36 (3.34)	−5.25 (4.6)	−7.34 (7.44)	−11.61 (7.42)
Median (range)	−0.50 (−8 to 6)	−5.25 (−8.5 to −2)	−4.69 (−24.88 to 2)	−10 (−22 to 0.75)
Zone II posterior (124 eyes)**	56 eyes	2 eyes	58 eyes	8 eyes
Mean (SD)	−0.63 (2.56)	0.88 (0)	−5.2 (5.77)	−10.42 (4.58)
Median (range)	0 (−13 to 2.5)	0.88 (0.88−0.88)	−4 (−19 to 3.5)	−11.5 (−15 to −2.63)

Notes:

* For zone I, the mean (SD) spherical equivalent refractions for the intravitreal bevacizumab group were −1.51 (3.42) D (median [range], −0.56 [−8.56 to 6] D), and for the laser group were −8.44 (7.57) D (median [range], −8.00 [−24.88 to 2] D) (P<0.001);

** for zone II posterior, the mean (SD) spherical equivalent refractions for the intravitreal bevacizumab group were −0.58 (2.53) D (median [range], 0 [−13 to 2.5] D), and for the laser group were −5.83 (5.87) D (median [range], −4.88 [−19 to 3.50] D) (P<0.001). Reproduced with permission from JAMA Ophthalmol. 2014;132(11):1327–1333. Copyright©2014 American Medical Association. All rights reserved.¹

Abbreviation: SD, standard deviation.

Figure 3 Percentage of eyes ≥−5 D in ETROP and BEAT-ROP by ROP severity at treatment.

Notes: Percentage of eyes with myopia ≥−5 D in the ETROP and BEAT-ROP clinical trials at ages 3 and 2.5 years, respectively. Data presented according to ROP severity at treatment (threshold, high-risk prethreshold, low-risk prethreshold, and all stage 3+) by treatment modality utilized (laser and IVB) in the respective clinical trials. Data from ETROP,³ and BEAT-ROP.¹
Abbreviations: ROP, retinopathy of prematurity; IVB, intravitreal bevacizumab.

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